BACKGROUND: Deep brain stimulation (DBS) in patients with severe, refractory Tourette syndrome (TS) has demonstrated promising but variable results thus far. The thalamus and anteromedial globus pallidus internus (amGPi) have been the most commonly stimulated sites within the cortico-striato thalamic circuit, but an optimal target is yet to be elucidated.

OBJECTIVES: This study of 15 patients with long-term amGPi DBS for severe TS investigated whether a specific anatomical site within the amGPi correlated with optimal clinical outcome for the measures of tics, obsessive compulsive behaviour (OCB), and mood.

METHODS: Validated clinical assessments were used to measure tics, OCB, quality of life, anxiety, and depression before DBS and at the latest follow-up (17-82 months). Electric field simulations were created for each patient using information on electrode location and individual stimulation parameters. A subsequent regression analysis correlated these patient-specific simulations to percentage changes in outcome measures in order to identify any significant voxels related to clinical improvement.

RESULTS: A region within the ventral limbic GPi, specifically on the medial medullary lamina in the pallidum at the level of the AC-PC, was significantly associated with improved tics but not mood or OCB outcome.

CONCLUSIONS: This study adds further support to the application of DBS in a tic-related network, though factors such as patient sample size and clinical heterogeneity remain as limitations and replication is required.

Background: Deep brain stimulation (DBS) systems in current mode and new lead designs are recently available. To switch between DBS-systems remains complicated as clinicians may lose their reference for programming. Simulations can help increase the understanding.

Objective: To quantitatively investigate the electric field (EF) around two lead designs simulated to operate in voltage and current mode under two time points following implantation.

Methods: The finite element method was used to model Lead 3389 (Medtronic) and 6148 (St Jude) with homogenous surrounding grey matter and a peri-electrode space (PES) of 250 μm. The PES-impedance mimicked the acute (extracellular fluid) and chronic (fibrous tissue) time-point. Simulations at different amplitudes of voltage and current (n=236) were performed using two different contacts. Equivalent current amplitudes were extracted by matching the shape and maximum EF of the 0.2 V/mm isolevel.

Results: The maximum EF extension at 0.2 V/mm varied between 2-5 mm with a small difference between the leads. In voltage mode EF increased about 1 mm at acute compared to the chronic PES. Current mode presented the opposite relationship. Equivalent EFs for lead 3389 at 3 V were found for 7 mA (acute) and 2.2 mA (chronic).

Conclusions: Simulations showed a major impact on the electric field extension between postoperative time points. This may explain the clinical decisions to reprogram the amplitude weeks after implantation. Neither the EF extension nor intensity is considerably influenced by the lead design.

New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode.

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome

The success of the deep brain stimulation (DBS) therapy relies primarily in the localization of the implanted electrode, implying the need of utmost accuracy in the targeting process. Intraoperative microelectrode recording and stimulation tests are a common procedure before implanting the permanent DBS lead to determine the optimal position with a large therapeutic window where side effects are avoided and the best improvement of the symptoms is achieved. Differences in dimensions and operating modes exist between the exploration and the permanent DBS electrode which might lead to different stimulation fields, even when ideal placement is achieved. The aim of this investigation is to compare the electric field (EF) distribution around the intraoperative and the chronic electrode, assuming that both have exactly the same position.

METHODS

3D models of the intraoperative exploration electrode and the chronically implanted DBS lead 3389 (Medtronic Inc., USA) were developed using COMSOL 5.2 (COMSOL AB, Sweden). Patient-specific MR images were used to determine the conductive medium around the electrode. The exploration electrode and the first DBS contact were set to current and voltage respectively (0.2mA(V) - 3 mA(V) in 0.1 mA(V) steps). The intraoperative model included the grounded guide tube used to introduce the exploration electrode; for the chronic DBS model, the outer boundaries were grounded and the inactive contacts were set to floating potential considering a monopolar configuration. The localization of the exploration and the chronic electrode was set according to the planned trajectory. The EF was visualized and compared in terms of volume and extension using a fixed isocontour of 0.2 V/mm.

RESULTS

The EF distribution simulated for the exploration electrode showed the influence of the parallel trajectory and the grounded guide tube. For an amplitude of e.g. 2 mA/2 V, the EF extension of the intraoperative was 0.6 mm larger than the chronic electrode at the target level; the corresponding difference in volume was 76.1 mm3.

CONCLUSION

Differences in the EF shape between the exploration and the chronic DBS electrode have been observed using patient-specific models. The larger EF extension obtained for the exploration electrode responds to its higher impedance and the use of current controlled stimulation. The presence of EF around the guide tube and the influence of the parallel trajectory require further experimental and clinical evaluation.

Objective: To quantitatively compare the electric field generated by voltage and current controlled deep brain stimulation systems.

Background: Traditionally deep brain stimulation (DBS) systems have used voltage control however more recently, current controlled systems have been approved to treat Parkinson's disease and related movement disorders. In the endeavor of understanding the behavior of DBS systems a common approach is the use of computer models suitable to simulate the electric field, current density and other related electric parameters.

Methods: 2D finite element models based on commercially available DBS systems have been built for each system: I. Model 3389, Medtronic Inc., USA for voltage control; and II. Model 6142, St Jude Medical Inc. USA for current control. The brain tissue has been simplified to homogeneous and isotropic medium. The electric settings correspond to a monopolar configuration, using one of the four contacts available as the active electrode and the outer boundary of the tissue as the reference. Three simulations were performed to mimic different stages of the leads implantation: a) an original stage where the brain tissue is considered as pure gray matter, b) an acute stage that simulates the leakage of cerebral spinal fluid immediately after the electrodes' insertion; and c) a chronic stage mimicking fibrous tissue created around the electrodes some weeks after implantation. Both systems were submitted to the same conditions using as active electrode the third contact from the tip of the lead. The comparison is based on the maximal distance reached by the isopotential of 0.2 V/mm.

Results: The simulations showed that voltage controlled stimulation systems are more susceptible to changes in the electrical conductivity of the medium i.e. change over time of the tissue around the electrode. This agrees with the adjustment of the stimulation amplitude often necessary a few weeks postoperatively. Current controlled stimulation in turn, presented a linear behavior of the distance reached at different stimulation amplitudes at all stages.

Conclusions: Current controlled stimulation might be a good option due to its linear behavior over time, nevertheless more studies including a more realistic brain model, different designs of DBS electrodes and different electric parameter, are needed to encourage the use of this type of systems.

Since the introduction of deep brain stimulation (DBS) the technique has been dominated by Medtronic sys-tems. In recent years, new DBS systems have become available for patients, and some are in clinical trials. The present study aims to evaluate three DBS leads operated in either voltage or current mode. 3D finite element method (FEM) models were built in combination with a neuron model for this purpose. The axon diameter was set to D = 5 μm and simulations performed in both voltage (0.5-5 V) and current (0.5-5 mA) mode. The evaluation was achieved based on the distance from the lead for neural activation and the electric field (EF) extension at 0.1 V/mm. The results showed that the neural activation distance agrees well between the leads with an activation distance dif-ference less than 0.5 mm. The shape of the field at the 0.1 V/mm isopotential surface in 3D is mostly spherical in shape around the activated section of the steering lead.

SINCE the introduction of deep brain stimulation (DBS) about 20 years ago, the stimulation technique has been dominated by Medtronic DBS-system setup. In recent years, new DBS systems have become available, of which some are in clinical trials or available to patients [1]. In the present study three different lead designs are investigated via computer simulation:

Medtronic 3389, St. Jude 6148 and Sapiens SureStim. The aim was to compare the neural activation distance and the electric field (EF) maximum spatial extension for each lead.

A 3D finite element method model was built using COMSOL Multiphysics 4.4a (COMSOL AB, Stockholm, Sweden) to simulate the electric potential around the DBS lead. Brain tissue was modelled as a homogeneous volume of grey matter (electric conductivity of 0.09 S/m). The electrode-tissue interface was modelled with a 250μm thick peri-electrode space mimicking the fibrous tissue which covers the lead at the chronic stimulation stage (σ = 0.06S/m, equivalent to white matter electric conductivity). The stimulation amplitude was set to 1V in monopolar configuration using C1 electrode or equivalent in all cases. Each simulated electric potential distribution was exported to MatLab (The MathWorks, USA) and used as input to a cable neuron simulation.

An axon cable model with 21 nodes based on the concept by Åström et al., [2] was set up in MatLab and combined with the exported field distributions. The model considered a 5 μm thick neuron, a pulse width of 60 μs and a drive potential ranging from 0.5 V to 5 V in 0.5 V steps.

The SureStim lead results showed a shorter neural activation distance and EF extension. The distance to the isolevel of 0.2 V/mm is close to the neural activation distance at each stimulation amplitude, and we conclude that the electric field is a suitable predictor to visualize the stimulated regions.

Microdialysis makes possible in vivo estimation of endogenous and exogenous substances in the dermal extracellular space. Insertion of the microdialysis probe and its subsequent presence in the skin may affect both the reactivity of the skin test site and the measurement of target substances. Laser Doppler flowmetry is a non-invasive method for estimating cutaneous blood flow. A further development of this technique, laser Doppler perfusion imaging, has been used to study the time course of the circulatory changes caused in the area of microdialysis probe insertion. Laser Doppler perfusion imaging was performed prior to, during, and after microdialysis probe insertion in the skin of the ventral forearm in three subjects. Probe insertion caused an increase in skin blood perfusion in the whole test area. About 15 min after probe insertion, the flare, which is presumed to be of chiefly axon reflex origin, began to subside and the circulatory response could be seen to center around the site of insertion and the tip of the probe. Skin perfusion levels had returned to near normal levels within 60 min. Local anesthesia of the point of guide insertion inhibited the flare, but did not affect circulatory reactivity in the skin nearby. Both microdialysis and laser Doppler perfusion imaging seem to be promising new methods in dermatologic research.

A novel bioanalytical in vivo sampling technique, cutaneous microdialysis, was used to follow the chronology of skin histamine release in 3 patients with cold urticaria and in 2 healthy volunteers. Laser Doppler perfusion imaging was used simultaneously to monitor the skin circulatory response. Microdialysis samples were collected at 10-min intervals and analysed by radioimmunoassay technique. Fifty minutes after probe insertion, the ventral forearm skin in the area of the dialysis membrane was provoked for 5-15 min with a 25 x 40 mm ice cube covered with plastic foil. In the cold urticaria patients, an up to 80-fold increase of histamine was observed, with peak levels 20-30 min after challenge. Histamine levels then fell to reach "baseline" levels within 50 min. In the healthy subjects, the histamine increase was earlier, less pronounced and of shorter duration. Cutaneous microdialysis and laser Doppler imaging offer new possibilities for the chronological multiparameter assessment of inflammatory skin disorders in vivo.

Diffuse reflectance spectroscopy as a method for improving intracerebral guidance during functional neurosurgery has been investigated. An optical probe was developed for measurements during stereotactic and functional neurosurgery in man. The aim of the study was to investigate the spectral differences between white and grey matter and between white matter and functional targets. Diffuse reflectance spectroscopy measurements in ten patients were recorded at incremental steps towards and in three different functional targets (STN, GPi and Zi). The recorded spectra along the trajectory were sorted into white or grey matter, based on preoperative MRI images or the recorded spectral shape and intensity. The difference between tissue types was calculated as a quotient. Significant intensity differences between white and grey matter were found to be at least 14% (p < 0.05) and 20% (p < 0.0001) for MRI and spectral-sorted data respectively. The reflectance difference between white matter and the functional targets of GPi was higher than for STN and Zi. The results indicate that diffuse reflectance spectroscopy has a potential to be developed to a suitable complement to other intracerebral guidance methods.

The aim of this study was to evaluate in vivo a laser Doppler measurement system in porcine brain tissue during thermal lesioning. A 2-mm monopolar radiofrequency lesioning electrode was equipped with optical fibers in order to monitor the lesioning procedure. Laser Doppler and backscattered light intensity signals were measured along the electrode trajectory and during bilateral lesioning in the central gray (70, 80 and 90°C, n = 14). The time course of the coagulation process could be followed by optical recordings. Two separate groups of tissue were identified from the intensity signals. The changes in the perfusion levels in both groups displayed significant changes (p < 0.05, n = 48) at all temperature settings, while backscattered light intensity was significant for only one group at the different temperatures (p < 0.05, n = 39). These results indicate that optical measurements correlate with lesion development in vivo. The study also indicates that it is possible to follow the lesioning process intra-operatively.

Radiofrequency (RF) lesioning in the human brain is a commonsurgical therapy for relieving severe pain as well as formovement disorders such as Parkinsonia. During the procedure a smallelectrode is introduced by stereotactic means towards a target arealocalized by CT or MRI. An RF-current is applied throughthe electrode tip when positioned in the target area. Thetissue in the proximity of the tip is heated bythe current and finally coagulated.The overall aim of this studywas to improve the RF-technique and its ability to estimatelesion size by means of optical methods. Therefore, the opticaldifferences between white and gray matter, as well as lesionedand unlesioned tissue were investigated. Reflection spectroscopy measurements in therange of 450-800 nm were conducted on fully anesthetized pigsduring stereotactic RF-lesioning (n=6). Light from a tungsten lamp wasguided to the electrode tip through optical fibers, inserted alonga 2 mm in diameter monopolar RF-electrode. Measurements were performedin steps of 0-10 mm from the target in eachhemisphere towards the entry point of the skull. In thecentral gray of the porcine brain measurements were performed bothbefore and after the creation of a lesion. A totalof 55 spectra were collected during this study. Correlation totissue type was done using post-operative MR-images. The spectral signaturefor white and gray matter differs significantly for the entirespectral range of 450-800 nm. Pre- and post-lesioning reflection spectroscopyshowed the largest differences below 600 and above 620 nm,which implies that lasers within this wavelength range may beuseful for in-vivo measurements of tissue optical changes during RF-lesioning.

Radiofrequency(RF) lesioning in the human brain is one possible surgicaltherapy for severe pain as well as movement disorders. Oneobstacle for a safer lesioning procedure is the lack ofsize monitoring. The aim of this study was to investigateif changes in laser Doppler or intensity signals could beused as markers for size estimation during experimental RF lesioning.A 2 mm in diameter monopolar RF electrode was equippedwith optical fibers and connected to a digital laser Dopplersystem. The optical RF electrode's performance was equal to astandard RF electrode with the same dimensions. An albumin solutionwith scatterers was used to evaluate the intensity and laserDoppler signal changes during lesioning at 70, 80, and 90 °C.Significant signal changes were found for these three different clotsizes, represented by the temperatures (p<0.05, n=10). The volume, width, andlength of the created coagulations were correlated to the intensitysignal changes (r=0.88, n=30, p<0.0001) and to the perfusion signalchanges (r=0.81, n=30, p<0.0001). Both static and Doppler-shifted light canbe used to follow the lesioning procedure as well asbeing used for lesion size estimation during experimental RF lesioning.

Laser Doppler Perfusion Imaging (LDPI) is a method for visualization of tissue blood perfusion. A low power laser beam is used to step-wise scan a tissue area of interest and a perfusion estimate based on the backscattered, partially Doppler broadened, light is generated. Although the basic operating principle of LDPI is the same as that of conventional Laser Doppler Perfusion Monitoring (LDPM), significant differences exist between the implementation of the methods which must be taken into account in order to generate high quality perfusion images. The purpose of this study is to investigate the relevance of a number of LDPI design parameters, such as:

(1) The influence of artifact noise when using a continuously moving laser beam instead of a step-wise moving beam to scan the image.

(2) The signal processor output's dependency on the distance between the measurement object and the scanner head when using collimated laser light.

(3) The speed and mode of the scanning.

The results show a substantial rise in the noise level when using a continuously moving beam as opposed to a step-wise. Skin measurements using a collimated laser beam demonstrated an amplification factor dependency on the distance between the skin surface and the scanner head not present when using a divergent laser beam. The scanning speed is limited by the trade-off between the Doppler signal lower cut-off frequency and the image quality.

The laser Doppler technique is used to assess tissue perfusion. Traditionally an integrated, ω-weighted (first-order filter) power spectrum is used to estimate perfusion. In order to be able to obtain selective information about the flow in vessels with different blood cell velocities, higher order filters have been implemented, investigated, and evaluated. Theoretical considerations show that the output of the signal processor will depend on the flow speed, for a given concentration of blood cells, according to Sout∞νn where v is the average blood cell speed and n is the spectral filter order. An implementation of filters using zero-, first-, second-, and third-order spectral moments was utilized to experimentally verify the theory by using a laser Doppler perfusion imager. Two different flow models were utilized: A Plexiglas model was used to demonstrate the various signatures of the power spectrum for different flow speeds and filter orders, whereas a Delrin model was used to study the relationship between the flow velocity and the output of the signal processor for the different filters. The results show good agreement with theory and also good reproducibility. Recordings made on the skin of the wrist area demonstrated that the flow in small veins can be visualized by the use of higher spectral orders.

Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon.

METHODS:

The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants' verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training.

RESULTS:

The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate.

CONCLUSION:

The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displays in clinical scenarios involving fluorescence guidance and other areas for which categorized auditory display could be useful.

In this paper, we investigate the possibility of using accurate prediction models for the prediction of protoporphyrin bleaching dynamics to achieve photobleaching-insensitive methods to improve the evaluation of data in an existing clinical fluorescence-guided resection technique. To simulate the scenario, measurements were carried out in vivo on skin of healthy volunteers using a compact fiber-based fluorescence spectroscopy system. We have developed an effective method for the parameterization of sequences of bleaching spectra. We analyze convergence and decay rates with respect to initial conditions and excitation irradiance. We also discuss the consequences and the potential for bleaching-insensitive measurements and their applicability in a few examples from in vivo open brain surgery.

Microdialysis of the basal ganglia was recently used to study neurotransmitter levels in relation to deep brain stimulation. In order to estimate the anatomical origin of the obtained data, the maximum tissue volume of influence (TVImax) for a microdialysis catheter was simulated using the finite element method. This study investigates the impact of brain heterogeneity and anisotropy on the TVImax using diffusion tensor imaging (DTI) to create a second-order tensor model of the basal ganglia. Descriptive statistics showed that the maximum migration distance for neurotransmitters varied by up to 55% (n = 98,444) for DTI-based simulations compared with an isotropic reference model, and the anisotropy differed between different targets in accordance with theory. The size of the TVImax was relevant in relation to the size of the anatomical structures of interest, and local tissue properties should be accounted for when relating microdialysis data to their anatomical targets.

Microdialysis of the basal ganglia was recently used to study changes of neurotransmitter levels in relation to deep brain stimulation (DBS). In order to estimate the anatomical origin of the microdialysis data, the maximum tissue volume of influence (TVImax) for a microdialysis catheter was simulated and visualized using the finite element method (FEM). In the current study the impact of brain heterogeneity and anisotropy on the TVImax was investigated, using diffusion tensor imaging (DTI) to create a second-order tensor model of the basal ganglia. The results were presented using descriptive statistics, indicating that the mean radius of the TVImax varied by up to 0.5 mm (n = 98444) for FEM simulations based on DTI compared to a homogeneous and isotropic reference model. The internal capsule and subthalamic area showed significantly higher anisotropy (p < 0.0001, n = 600) than the putamen and the globus pallidus, in accordance with theory. It was concluded that the size of the TVImax remained small enough to be relevant in relation to the anatomical structures of interest, and that local tissue properties should be accounted for when relating the microdialysis data to their anatomical targets.

Microdialysis of the basal ganglia was used in parallel to deep brain stimulation (DBS) for patients with Parkinson’s disease. The aim of this study was to patientspecifically simulate and visualize the maximum tissue volume of influence (TVImax) for each microdialysis catheter and the electric field generated around each DBS electrode. The finite element method (FEM) was used for the simulations. The method allowed mapping of the anatomical origin of the microdialysis data and the electric stimulation for each patient. It was seen that the sampling and stimulation targets differed among the patients, and the results will therefore be used in the future interpretation of the biochemical data.

Microdialysis can be used in parallel to deep brain stimulation (DBS) to relate biochemical changes to the clinical outcome. The aim of the study was to use the finite element method to predict the tissue volume of influence (TVI(max)) and its cross-sectional radius (r (TVImax)) when using brain microdialysis, and visualize the TVI(max) in relation to patient anatomy. An equation based on Fick's law was used to simulate the TVI(max). Factorial design and regression analysis were used to investigate the impact of the diffusion coefficient, tortuosity and loss rate on the r (TVImax). A calf brain tissue experiment was performed to further evaluate these parameters. The model was implemented with pre-(MRI) and post-(CT) operative patient images for simulation of the TVI(max) for four patients undergoing microdialysis in parallel to DBS. Using physiologically relevant parameter values, the r (TVImax) for analytes with a diffusion coefficient D = 7.5 × 10(-6) cm(2)/s was estimated to 0.85 ± 0.25 mm. The simulations showed agreement with experimental data. Due to an implanted gold thread, the catheter positions were visible in the post-operative images. The TVI(max) was visualized for each catheter. The biochemical changes could thereby be related to their anatomical origin, facilitating interpretation of results.

OBJECTIVE : This study describes the production, under strictly standardized and controlled conditions, of radiofrequency lesions with identical neurogenerator settings: in vitro in two different albumin solutions (nongelatinous and gelatinous) and in vivo in the thalamus of the pig.

METHODS : The radiofrequency lesions were investigated in vitro by the use of a specially designed video system and in vivo by magnetic resonance imaging. Moreover, the size of the in vivo lesions was estimated with the use of histological sectioning. The statistical analysis included the calculation of a correlation coefficient for the length, width, and volume for each lesion estimation.

RESULTS : A high correlation (R = 0.96, P < 0.005; n = 14) was found between clot sizes in the two albumin solutions. Albumin clots generated in gelatinous albumin showed systematically larger volumes. In the pig, two concentric zones were seen in all magnetic resonance images and all histological preparations. The width correlation of the completely coagulated brain tissue (inner zones) was R = 0.94, P < 0.005, and n = 7. The corresponding correlation between magnetic resonance images and gelatinous albumin was R = 0.93, P < 0.005, and n = 7. As a rule, the in vitro clots were smaller than the outer zone but larger than the inner zone of the magnetic resonance imaging-recorded lesions for all of the electrode and temperature combinations tested. In vivo lesions generated with the same electrode and parameter settings showed high reproducibility.

CONCLUSION : The value of presurgical electrode tests to validate the electrode function and lesion size in vitro has become evident in this study, which shows a high correlation between the in vitro albumin clots and the in vivo lesions observed on magnetic resonance images.

The aim of this study was to develop a finite element model for simulation of the thermal characteristics of brain electrodes and to compare its performances with an in vitro experimental albumin model. Ten lesions were created in albumin using a monopolar electrode connected to a Leksell Neuro Generator and a computer-assisted video system was used to determine the size of the generated lesions. A finite element model was set up of the in vitro experiments using the same thermal properties. With a very simple heat source applied to the finite element model in the proximity of the upper part of the tip, a good agreement (no deviations in width and distance from tip but a deviation in length of −1.6 mm) with the in vitro experiments (width 4.6±0.1 mm and length 7.4±0.1 mm) was achieved when comparing the outline of the lesion. In addition, a gelatinous albumin-model was set up and compared to computer simulations resulting in deviations in width of −0.4 mm, length of −2.2 mm and distance from the tip of −0.1 mm. Hence, the utilisation of finite element model simulations may be a useful complement to in-vitro experiments.

A method for in-vitro size estimation of protein clots generated by brain electrodes is presented. Radiofrequency generated thermal brain lesions are widely used in functional neurosurgery and in-vitro tests are used to confirm the electrodes' ability to generate lesions. To be able to estimate the size of protein clots generated in-vitro by brain electrodes, a computer-assisted video system was set up. The size estimation is carried out by software using two captured images of the protein clot. The “true” length and width (9.5 mm) of a sphere as measured with a slide-caliper differed at the most 0.5 mm (5%) and 0.3 mm (3%) respectively, all random errors fall within 2s.d

Stereotactic radiofrequency (RF)-lesioning in the central part of the brain is performed on patients that, for instance, have severe movement or psychiatric disorders. The size of the generated lesion can to some extent be controlled by RF-generator settings such as temperature and time as well as the electrode configuration. Today, MR- imaging and CT are the essential diagnostic methods to confirm the lesion size in vivo. The aim of this study was to investigate whether it is possible to use changes in the reflected light intensity and laser Doppler flowmetry as a marker for size estimation during RF-lesioning.

Radiofrequency (RF) generated thermal brain lesions are widely used in functional neurosurgery. The size, shape and development of the lesions depends on system parameter settings and the electrode configuration. Difficulties in studying the effect of these factors in vivo stimulated us to develop an in vitro system for standardized comparison between different electrodes and physical parameters. A computer-assisted video system was set-up allowing continuous video recording of RF-generated coagulations in either a standard albumin solution or in the fresh white of a hen's egg as transparent test substrates. Ten lesions were made with each test electrode (two bipolar and three monopolar) in each of the two substrates at 70 degrees, 80 degrees and 90 degrees C (t = 60 sec). Due to the better homogeneity the lesions in the albumin solution were much more regular and reproducible. This made it possible to calculate the size (width 2.2 +/- 0.1 to 5.3 +/- 0.1 mm and length 3.0 +/- 0.1 to 8.7 +/- 0.3 mm) as well as the volume (8.5 +/- 1.4 mm3 to 133.5 +/- 26.8 mm3). It is concluded that this in vitro system offers a reproducible way to study and document the effect of different electrode configurations and RF-generator settings on the formation of a heat lesion. Even if the results are not directly applicable to the living human brain they give an estimate of the form and size of a coagulation lesion and can be of value for standardized comparisons between different electrodes.

Background: Phototesting based on a single exposure to a divergent ultraviolet B (UVB) beam with radially decreasing UVB doses can be used to determine an individual's minimal erythema dose (MED). Laser Doppler perfusion imaging (LDPI) data can be combined with dosimetry data to produce objective dose–response plots in addition to the MED. The aim of this study was to investigate whether the divergent beam protocol could be used to demonstrate and quantify the anti-inflammatory effects of clobetasol diproprionate (Dermovate®), pharmaceutical-grade acetone and a gel vehicle, applied after skin provocation by UVB.

Method: Sixteen Caucasian subjects were illuminated with the divergent beam on three areas close together on the left side of their upper backs. Two of the provoked areas on each subject were treated with acetone, gel vehicle or Dermovate®, and one area was left untreated as a control. Skin blood perfusion was assessed 6 and 24 h after UVB illumination using LDPI. The reaction diameter, the mean perfusion, and the average dose–response plots for each group and treatment were extracted from the LDPI data.

Results: Application of the topical steroid clobetasol diproprionate after UVB provocation markedly decreased the inflammatory response. Acetone and the gel vehicle also showed mild anti-inflammmatory effects in two of the parameters but not for the mean perfusion response. The mean diameter differences between controls and treated reactions had predominantly positive 99% confidence intervals. Analysis of the dose–response data at doses higher than the MED showed a linear relationship (0.89≤R2≤0.98) for all reactions but with lower gradients in treated reactions, mostly marked for clobetasol diproprionate.

Conclusions: The divergent beam protocol can be used to demonstrate and quantify the effects of topical agents on the UVB reaction, in terms of reaction diameter, mean perfusion and changes in dose–response characteristics. The dose–response approach seems to be applicable even in diagnostic testing of an individual patient's response to UVB.

Laser Doppler perfusion monitoring is a suitable method for microvascular blood perfusion measurements. When used on a moving tissue or organ, the Doppler signal arising from the moving blood cells may be distorted. ECG triggering of the laser Doppler signal can be used for reducing the influence from movements during measurements on the beating heart. The aim of this study was to determine the most appropriate triggering intervals during the cardiac cycle for online measurements. Recordings from thirteen coronary artery bypass graft (CABG) patients were included in the study. During surgery, the fibre-optic probe was passed through the chest wall and sutured to the left anterior ventricular wall with the probe tip inserted 3–5 mm into the myocardium. After the patient arrived at the intensive care unit a second measurement was initiated and lasted for about two hours. Before the probe was removed a third measurement was performed for about 5 minutes the following morning. A total of 97 data sequences were analysed and the intervals of low and stable perfusion signal were compared to the positions of the T and P peaks in the ECG.

It was found that the most appropriate time intervals were in late systole at the T peak [−3, 9] ms and just before the P peak [−28, -10] ms in late diastole. However, the position of these intervals may vary between individuals, because of e.g., abnormal cardiac motion. With the use of the appropriate interval online measurement of the myocardial perfusion on a beating heart appears possible.